With the HIV Prevention Treatment Network 052 study proving that early antiretroviral (ART) initiation reduces rates of HIV sexual transmission and clinical events, and with women making up 50% of people living with HIV globally, a better understanding of how women with HIV start, stay on and respond to ART and how this therapy impacts prevention, treatment, and care/cure of HIV/AIDS is needed. African American women continue to bear the largest burden of HIV disease among women, with disproportionately higher rates of new HIV infections, AIDS diagnoses, and mortality. The major goal of this proposal is to continue the high level of productivity of the Chicago WIHS Consortium (CWC) as both a clinical research site and as a consortium of scientific leaders with a track record of advancing our understanding of the evolving HIV epidemic in US women. We will continue to rapidly recruit and retain a representative cohort of women with and at risk for HIV, to collect th highest quality data in order to lead and pursue innovative epidemiologic analyses, and multidisciplinary investigations to characterize treated HIV disease in women. Over the WIHS-V five year period, we will continue to design, implement, synthesize, and disseminate findings from investigations which explore the dynamic and complex relationships between HIV, ART, viral suppression, sociodemographics, behaviors, mental illness, immune biomarkers, menopausal stage, and comorbidities rather than focusing on the impact of any one single factor. The CWC investigative team proposes to expand and retain the Chicago cohort and to apply analytic modeling to longitudinal social/behavioral, clinical, neurocognitive, and pathogenesis data to develop and test a gender specific prognostic index (WIHS Index). We aim to identify psychological, neuroendocrine, genetic, and immunologic predictors of HIV disease phenotypes, including those characterized by inflammation, activation, and cellular senescence and determine the association with clinical and pre-clinical measures of HIV associated non AIDS (HANA) co-morbidities. Since evidence suggests that potentially modifiable factors, such as untreated mental illness, chronic life stress, and use of addictive substances can contribute to inflammation and accelerate telomere shortening, a key molecular marker of cellular senescence, we will explore the interactions between psychiatric diagnoses, hormonal patterns, and markers of the innate and adaptive immune system. Given the high rates of these modifiable factors in our cohort, we propose a multi-site randomized controlled trial to test an evidence based computerized tailored intervention based on the Transtheoretical Model to address risk behaviors concurrently aimed at smoking cessation, improving ART adherence, and effectively managing stress, depression, and weight. Through these WIHS V efforts, we hope to identify new tools that can be used at all levels of HIV care (community, clinic, and laboratory) to empower clinicians and their female patients to improve the prognosis and lives of women with HIV.